Acute disseminated encephalomyelitis pathophysiology

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sujaya Chattopadhyay, M.D.[2]

The exact mechanism of acute disseminated encephalomyelitis is not determined. However, it is usually preceded by an environmental trigger, e.g. an infection or vaccination and affects individuals with a genetic predisposition.

• Acute disseminated encephalomyelitis is described as an autoimmune disorder, resulting in central nervous system demyelination.Enviromental stimuli activate cellular and humoral responses which cross-react with myelin autoantigens namely, myelin basic protein, myelin oligoendrocyte protein, proteolipid protein.
• In an alternative mechanism, post-vaccination and post-infective circulating immune complexes in the CNS give rise to an inflammatory reaction, resulting in increased vascular permeability and congestion. This disrupts the blood– brain barrier, allowing infiltration by antigens and mononuclear cells. They cause perivascular edema and hemorrhage which culminate in demyelination, necrosis and gliosis. Although typically observed in white matter, gray matter involvement is also seen in basal ganglia, thalamus and cerebral cortex^[2].
• Some of the vaccine-associated cases can be attributed to the contamination of the vaccine with CNS tissue, reported for the Semple vaccine for rabies^[3] and the vaccine strains of Japanese encephalitis^[4].

• CNS tissue is damaged by direct infection by a neurotropic pathogen, resulting in leakage of autoantigens through a disrupted blood-brain barrier.
• The auto-antigens are processed in systemic lymphatic organs, leading to tolerance breakdown and a self-reactive encephalitogenic T-cell response.
• Such activated T-cells perpetuate a vicious cycle of further CNS damage and inflammation.

• It is attributed to a structural or partial amino acid sequence homology between the foreign pathogen and the myelin proteins of the host.
• Antigen-presenting B cells or dendritic cells process the antigen at the site of inoculation, leading to T-cell stimulation, which may cross-activate production of antigen-specific B cells.
• Both T-cells and B-cells are capable to entering the CNS and encounters the indigenous myelin proteins during routine CNS surveillance.
• They may become reactivated by local antigen-presenting cells such as the microglia, inciting an inflammatory response against the presumed foreign antigen.
• Thus, the initial physiologic response culminates in detrimental autoimmunity.

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